Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on a standard enzymatic assay and calibration method, with no mention of AI or ML techniques.

Therapeutic

No.
This device is an in vitro diagnostic test used for the quantitative measurement of ammonia in human plasma, which aids in diagnosis. It does not provide therapy or treatment for a disease or condition.

Diagnostic

Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "The AMM method is an in vitro diagnostic test for the quantitative measurement of ammonia in human plasma on the Dimension Vista® System. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome." Additionally, the "Device Description" calls it an "in vitro diagnostic device."

SaMD (Software as a Medical Device)

No

The device description clearly states it is an "in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge" and a "two level, liquid calibrator," indicating it includes physical components beyond software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states the AMM method is an "in vitro diagnostic test for the quantitative measurement of ammonia in human plasma." It also states the CHEM 3 CAL is an "in vitro diagnostic product for the calibration of Ammonia (AMM)... methods."
Device Description: The description of both the AMM Flex® reagent cartridge and the CHEM 3 CAL refers to them as "in vitro diagnostic device" and "in vitro diagnostic product" respectively.
Nature of the Test: The test measures a substance (ammonia) in a biological sample (human plasma) to aid in the diagnosis and treatment of medical conditions (severe liver disorders). This is the core function of an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The AMM method is an in vitro diagnostic test for the quantitative measurement of ammonia in human plasma on the Dimension Vista® System. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome.

The CHEM 3 CAL is an in vitro diagnostic product for the calibration of Ammonia (AMM), Carbon Dioxide (CO2) and Ethyl Alcohol (ETOH) methods on the Dimension Vista" System.

Product codes (comma separated list FDA assigned to the subject device)

JIF, JIX

Device Description

The Dimension Vista® Ammonia assay (AMM) is an enzymatic method that uses glutamate dehydrogenase (GLDH) and a stabilized NADPH analog. Ammonia reacts with a-ketoglutarate and reduced cofactor to form L-glutamate and the cofactor. The reaction is catalyzed by glutamate dehydrogenase. The decrease in absorbance due to the oxidation of the reduced cofactor is monitored at 340/700 nm and is proportional to the ammonia concentration.

GLDH NHa* + reduced cofactor -> -> - L-glutamate + cofactor + H2O a-ketoglutarate +

The Dimension Vista® Ammonia (AMM) Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge for use on the Dimension Vista® System. Flex® reagent cartridges hold reagents for a test method. Each Dimension Vista® Flex · has twelve wells.

| Wellsa

1 - 12	Form	Ingredient	Concentrationb,c	Source
Liquid	α-ketoglutarate
GLDH
NADPH	10 mmol/L
≥ 24 KU/L
0.2 mmol/L	Microbial

Wells are numbered consecutively from the wide end of the cartridge. a.

Nominal value per well in a cartridge. ﻀ

Contain buffers, stabilizers and preservatives. C.

Reagent preparations are performed automatically on the instrument. A barcode label on the cartridge identifies the test method, lot number, expiration date and maximum number of tests for which the cartridge can supply reagent.

The Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) is a two level, liquid calibrator. It is packaged as a kit of six vials with 2.5 mL per vial. The product is a multi-analyte, aqueous product containing ammonium bicarbonate, sodium carbonate and ethyl alcohol. This product is sold separately from the Flex® reagent cartridge.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Method Comparison: Split sample comparison between the Dimension Vista® Ammonia (AMM) assay and the Dimension Vista Ammonia (AMON) assay gave the following correlation statistics, when tested with patient samples:
Slope: 1.03
Intercept: 13.6 µg/dL [8.0 µmol/L]
Correlation Coefficient (r): 0.993
n: 100

Plasma Equivalency Comparison: Comparison testing of 49 fresh matched lithium heparin and EDTA plasma samples were tested on the Dimension Vista® System.
Slope: 0.96
Intercept: 3.3 [2.0]
Correlation Coefficient (r): 1.00
n: 49

Precision: Performed in accordance with CLSI EP5-A2 using three levels of Liquicheck™ Ethanol/Ammonia control over 20 days.
Level 1: Mean 44 [26], Repeatability SD 2.7[1.6] (%CV 6.1), Within-Lab SD 3.3[1.9] (%CV 7.5)
Level 2: Mean 186 [109], Repeatability SD 2.3 [1.4] (%CV 1.2), Within-Lab SD 3.2 [1.9] (%CV 1.7)
Level 3: Mean 563 [331], Repeatability SD 3.5 [2.1] (%CV 0.6), Within-Lab SD 5.0 [2.9] (%CV 0.9)

Linearity: The analytical measurement range was determined to be 17 - 1277 µg/dL [10 - 750 µmol/L].

Analytical Specificity/Interferences: Evaluated according to CLSI EP7-A2. Bias exceeding 10% is considered interference.
Substances showing >10% bias at 85 [50] µg/dL ammonia: Hemoglobin (+12%), Conjugated Bilirubin (-16%), Lipemia (+13%), Albumin (49%), Cholesterol (65%), Creatinine (34%), Dextran 40 (13%), Immunoglobulin G (30%), Uric Acid (43%).
Substances showing >10% bias at 426 [250] µg/dL ammonia: Hemoglobin (+17%), Albumin (15%), Cholesterol (34%), Dextran 40 (16%), Hemoglobin (17%), Uric Acid (17%).
Note: Triglycerides "Tripped a test report message; therefore magnitude of the interference could not be determined." at 85 [50] µg/dL.

Limit of Blank, Limit of Determination and Limit of Quantitation: Evaluated in accordance with CLSI EP17-A.
LoB: 4 µg/dL [2 µmol/L]
LoD: 15 µg/dL [9 µmol/L]
LoQ: 17 µg/dL [10 µmol/L]

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K863840, K062334

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1065 Ammonia test system.

(a)
Identification. An ammonia test system is a device intended to measure ammonia levels in blood, serum, and plasma, Ammonia measurements are used in the diagnosis and treatment of severe liver disorders, such as cirrhosis, hepatitis, and Reye's syndrome.(b)
Classification. Class I.

Summary

0

K123677

510k Summary

MAR 0 7 2013

Dimension Vista® Ammonia Flex® reagent cartridge (AMM) Dimension Vista® Chem 3 Calibrator (CHEM 3 CAL)

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

1. 510(k) Number

Applicant: Rose T. Marinelli Siemens Healthcare Diagnostics, Inc. P.O. Box 6101, Newark, DE 19714-6101 Office Number: 302-631-8805; Fax Number: 302-631-6299
Date: November 28, 2012

4. Proprietary and Established Names:

Dimension Vista® Ammonia Flex® reagent cartridge, (AMM) Dimension Vista® Chem 3 Calibrator (CHEM 3 CAL)

5. Regulatory Information:

Ammonia (AMM) Flex® reagent cartridge

Requlation section: 21 CFR 862.1065 Enzymatic Method, Ammonia Classification: Class I Product Code: JIF Panel: Clinical Chemistry

Chemistry 3 Calibrator (CHEM 3 CAL)

Regulation section: 21 CFR 862.1150 Calibrator, Secondary Classification: Class II Product Code: JIX Panel: Clinical Chemistry

6. Predicate Devices:

The predicate device used to demonstrate substantial equivalence to the Dimension® Ammonia (AMM) Flex® reagent cartridge is the Dimension® Ammonia (AMON) previously cleared under K863840.

The predicate device used to demonstrate substantial equivalence to the Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) is the Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) previously cleared under K062334.

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7. Device Description:

The Dimension Vista® Ammonia assay (AMM) is an enzymatic method that uses glutamate dehydrogenase (GLDH) and a stabilized NADPH analog. Ammonia reacts with a-ketoglutarate and reduced cofactor to form L-glutamate and the cofactor. The reaction is catalyzed by glutamate dehydrogenase. The decrease in absorbance due to the oxidation of the reduced cofactor is monitored at 340/700 nm and is proportional to the ammonia concentration.

GLDH NHa* + reduced cofactor -> -> - L-glutamate + cofactor + H2O a-ketoglutarate +

The Dimension Vista® Ammonia (AMM) Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge for use on the Dimension Vista® System. Flex® reagent cartridges hold reagents for a test method. Each Dimension Vista® Flex · has twelve wells.

| Wellsa

1 - 12	Form	Ingredient	Concentrationb,c	Source
Liquid	$\alpha$-ketoglutarate
GLDH
NADPH	10 mmol/L
$\geq$ 24 KU/L
0.2 mmol/L	Microbial

Wells are numbered consecutively from the wide end of the cartridge. a.

Nominal value per well in a cartridge. ﻀ

Contain buffers, stabilizers and preservatives. C.

Reagent preparations are performed automatically on the instrument. A barcode label on the cartridge identifies the test method, lot number, expiration date and maximum number of tests for which the cartridge can supply reagent.

The Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) is a two level, liquid calibrator. It is packaged as a kit of six vials with 2.5 mL per vial. The product is a multi-analyte, aqueous product containing ammonium bicarbonate, sodium carbonate and ethyl alcohol. This product is sold separately from the Flex® reagent cartridge.

8. Intended Use:

The AMM method is an in vitro diagnostic test for the quantitative measurement of ammonia in human plasma on the Dimension Vista® System. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome.

The CHEM 3 CAL is an in vitro diagnostic product for the calibration of Ammonia (AMM), Carbon Dioxide (CO2) and Ethyl Alcohol (ETOH) methods on the Dimension Vista" System.

9. Indication(s) for Use:

The AMM method is an in vitro diagnostic test for the quantitative measurement of ammonia in human plasma on the Dimension Vista® System. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome.

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The CHEM 3 CAL is an in vitro diagnostic product for the calibration of Ammonia (AMM), Carbon Dioxide (CO2) and Ethyl Alcohol (ETOH) methods on the Dimension Vista" System.

10. Substantial Equivalence Information:

Both the Dimension Vista® Ammonia Flex® reagent cartridge (AMM) assay and the predicate Dimension® Ammonia Flex® reagent cartridge (AMON) assay employ prepackaged reagents for use on automated clinical chemistry test systems. A comparison of the similarities and differences between the devices is provided in the following tables.

Note: Siemens has decided to offer our customers both conventional units and Systéme International d'Unités (SI units) in the Instructions for Use (IFU). The predicate, Dimension® Ammonia (AMON) assay results are reported in SI Units only. All data supplied in Appendix C will include both conventional units and SI Units for ease of review. Raw data was collected from the instruments in SI units and the conventional units were calculated using the following equation: ug/dL x 0.587 = [umol/L].

| Feature | New Device : Dimension Vista®
Ammonia Flex® reagent
cartridge (AMM) | Predicate: Dimension®
Ammonia Flex® reagent
cartridge (AMON) K863840 |
|--------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The AMM method is an in vitro
diagnostic test for the quantitative
measurement of ammonia in
human plasma on the Dimension
Vista® System. Ammonia
measurements are used in the
diagnosis and treatment of severe
liver disorders such as cirrhosis,
hepatitis and Reye's syndrome. | The AMON method used on the
Dimension® clinical chemistry
system is an in vitro diagnostic
test intended for the quantitative
determination of ammonia in
human plasma. |
| Format | Prepackaged for use on an
automated system. | Prepackaged for use on an
automated system. |
| Measurement | Bichromatic Rate | Bichromatic Rate |

Similarities for Dimension Vista® AMM assay:

Differences for Dimension Vista® AMM assay:

| Feature | New Device: Dimension Vista®
Ammonia Flex® reagent
cartridge (AMM) | Predicate: Dimension®
Ammonia Flex® reagent
cartridge (AMON) K863840 |
|--------------------|--------------------------------------------------------------------------|----------------------------------------------------------------------------|
| Measuring
Range | 17-1277 µg/dL [10 - 750 µmol/L] | 0 - 1000 µmol/L |
| Sample Type | Plasma (Lithium Heparin and
EDTA) | Plasma (EDTA, Lithium Heparin,
Sodium Fluoride) |
| Reagent Form | Liquid | Tablet |
| Units | µg/dL and µmol/L | µmol/L |
| Sample Size | 20 µL | 53 µL |

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Similarities for Dimension Vista® CHEM 3 CAL:

| Feature | New Device: Dimension Vista®
Chem 3 Calibrator (CHEM 3 CAL) (KC130A) | Predicate: Dimension Vista®
Chem 3 Calibrator (CHEM 3 CAL) (KC130) |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The CHEM 3 CAL is an in vitro
diagnostic product for the
calibration of Carbon Dioxide
(CO2) and Ethyl Alcohol (ETOH)
methods on the Dimension Vista®
System. | The CHEM 3 CAL is an in vitro
diagnostic product for the
calibration of Carbon Dioxide
(CO2) and Ethyl Alcohol (ETOH)
methods on the Dimension Vista®
System. |
| Preparation | Liquid: Ready to use | Liquid: Ready to use |
| Storage | 2 – 8 °C | 2 - 8 °C |
| Traceability | AMM - ASC Grade Ammonium
Sulfate
ECO2 - NIST SRM 351
ETOH - USP Grade Ethyl
Alcohol | AMM - ASC Grade Ammonium
Sulfate
ECO2 - NIST SRM 351
ETOH - USP Grade Ethyl Alcohol |
| Matrix | Aqueous product containing ethyl
alcohol, ammonium bicarbonate
and sodium carbonate. | Aqueous product containing ethyl
alcohol, ammonium bicarbonate
and sodium carbonate. |
| Target
Concentrations | EC02 - CAL A - 0 mmol/L
CAL B - 50 mmol/L
ETOH - CAL A - 0 mg/dL
CAL B - 315 mg/dL | EC02 - CAL A - 0 mmol/L
CAL B - 50 mmol/L
ETOH - CAL A - 0 mg/dL
CAL B - 315 mg/dL |

Differences for Dimension Vista® CHEM 3 CAL

.

| Feature | New Device: Dimension Vista®
Chem 3 Calibrator (CHEM 3
CAL) (KC130A) | Predicate: Dimension Vista®
Chem 3 Calibrator (CHEM 3
CAL) (KC130) |
|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The CHEM 3 CAL is an in vitro
diagnostic product for the
calibration of Ammonia (AMM
method on the Dimension Vista®
System. | The CHEM 3 CAL is an in vitro
diagnostic product for the
calibration of Ammonia (AMON),
method on the Dimension Vista®
System. |
| Target
Concentrations
for AMM | Calibrator A: 0 μg/dL[μmol/L]
Calibrator B: 1405 μg/dL
[825 μmol/L] | Calibrator A: 0 μmol/L
Calibrator B: 1000 μmol/L |
| Units | μg/dL and μmol/L | μmol/L |

:

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11. Standard/Guidance Document Reference:

· Evaluation of Precision Performance of Quantitative Measurement in Methods; Approved Guideline (EP5-A2)
· Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline (EP6-A)
· Interference Testing in Clinical Chemistry; Approved Guideline (EP7-A2)
· Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (EP9-A2)
· Protocols for Determination of Limits of Detection and Quantitation; Approved Guideline (EP17-A)
· Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline (C28-A3)
· Evaluation of Stability of In-Vitro Diagnostic Reagents; Approved Guideline (EP25-A)

12. Performance Characteristics

The following data represent typical performance for the Dimension Vista® System and were collected on a Dimension Vista® 1500 System.

Method Comparison

Split sample comparison between the Dimension Vista® Ammonia (AMM) assay and the Dimension Vista Ammonia (AMON) assay gave the following correlation statistics, when tested with patient samples:

| Dimension
Vista® | Predicate | Slope | Intercept
µg/dL [µmol/L] | Correlation
Coefficient (r) | n |
|---------------------|--------------------|-------|-----------------------------|--------------------------------|-----|
| AMM | Dimension®
AMON | 1.03 | 13.6 µg/dL
[8.0 µmol/L] | 0.993 | 100 |

Dimension Vista® Ammonia (AMM) vs. Predicate

Plasma Equivalency Comparison

To demonstrate equivalency between lithium heparin plasma for Dimension Vista " AMM assay, comparison testing of 49 fresh matched lithium heparin and EDTA plasma samples were tested on the Dimension Vista® System and gave the following linear regression statistics:

Plasma Equivalency Comparison Data

| Lithium
Heparin vs. | Slope | Intercept
μg/dL [μmol/L] | Correlation
Coefficient (r) | n |
|------------------------|-------|-----------------------------|--------------------------------|----|
| EDTA | 0.96 | 3.3 [2.0] | 1.00 | 49 |

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Reference Interval (Expected Values)

The reference interval of 19 - 54 ug/dL [11 - 32 umol/L] for the predicate was validated for use with the Dimension Vista® Ammonia (AMM) assay by transference following CLSI C28-A3 Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory - Approved Guideline - Third Edition. The literature reference used was the Textbook of Clinical Chemistry by NW Tietz; WB Saunders Co., Philadelphia, PA; pages 1487-1488.

Expected Values: 19 - 54 µq/dL [11 - 32 µmol/L]

Precision

Precision testing was performed in accordance with CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition. Samples consisted of three levels of Liquicheck™ Ethanol/Ammonia control. Testing was performed over 20 days, two separate runs with two test samples for each test material. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP5-A2. The data are summarized in the following Dimension® Ammonia (AMM) Summary Table:

| Material | Mean
µg/dL [ µmol/L] | | Standard Deviation (%CV)
Repeatability
µg/dL [µmol/L] %CV | | Within-Lab |
|------------------------------------|-------------------------|-------|-----------------------------------------------------------------|-------|-----------------|
| Liquichek™ Ethanol/Ammonia control | | | | | |
| Level 1 | 44 | [26] | 2.7[1.6] | (6.1) | 3.3[1.9] (7.5) |
| Level 2 | 186 | [109] | 2.3 [1.4] | (1.2) | 3.2 [1.9] (1.7) |
| Level 3 | 563 | [331] | 3.5 [2.1] | (0.6) | 5.0 [2.9] (0.9) |

Linearity

The linear range was determined according to CLSI EP-6A. Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline. Based on the results of this testing and the Limit of Detection testing on the Dimension Vista" System, the analytical measurement range was determined to be 17 - 1277 µg/dL [10 - 750 µmol/L].

6

Image /page/6/Figure/0 description: The image is a scatter plot comparing observed AMM to expected AMM, both measured in micrograms per deciliter. The data points form a nearly perfect linear relationship. A line of best fit is shown, with the equation y = 0.99x + 3.74 and an R-value of 1.00, indicating a very strong positive correlation.

Analytical Specificity/Interferences

Interfering Substances

The AMM assay was evaluated for interference according to CLSI EP7-A2 Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference.

| Substance Tested | Substance Concentration | Ammonia
µg/dL [µmol/L] | Bias
% |
|-----------------------------|----------------------------------------------------|---------------------------|------------|
| Hemoglobin
(hemolysate) | 75 mg/dL [0.05 mmol/L]
500 mg/dL [0.62 mmol/L] | 85 [50]
426 [250] | +12
+17 |
| Bilirubin
(unconjugated) | 80 mg/dL [1026 µmol/L] | 85 [50]
426 [250] |